Example 5: Preparation of methyl 2-[4-(4-bromo-2-fluorophenoxy)phenoxy]propionate (STR29)
1. 2-Fluorophenol (22.4 g, 0.2 mol) was dissolved in dichloromethane (250 mL) under ice bath conditions and cooled to about 3 °C. 2.
2. bromine (31.97 g, 0.2 mol) was added slowly, keeping the reaction temperature at ice bath conditions.
3. the reaction mixture was stirred at ice bath temperature for 2 hours, followed by continued stirring at room temperature for 1 hour.
4. the reaction mixture was quenched by pouring into water (600 mL) containing excess sodium bisulfite.
5. The organic phase was separated and the aqueous phase was washed with additional dichloromethane (200 mL).
6. The organic extracts were combined, washed with saturated sodium bicarbonate solution and subsequently dried over anhydrous magnesium sulfate.
7. The solvent was removed by evaporation to afford the target product 2-fluoro-4-bromophenol as a colorless oil (34.5 g, 90% yield).
8. The structure of the product was confirmed to be as expected by NMR hydrogen spectroscopy (CDCl3).
[1] Patent: US4642338, 1987, A
[2] Patent: US4725683, 1988, A
[3] Patent: US4808750, 1989, A
[4] Patent: US4550192, 1985, A
[5] Chemistry - A European Journal, 2017, vol. 23, # 5, p. 1044 - 1047
